This Program Project Grant application has been initiated in order to utilize the expertise in our institution to clarify the mechanisms by which bone cell function is disordered in diseases of the oral cavity. It is our contention that the mechanisms by which disease process of the oral cavity affect alveolar bone is by the generation of soluble factors which stimulate bone cells. The specific aims of this application are to identify the mechanisms by which disease processes in the oral cavity affect bone resorbing and bone forming cells, and our plan is to use in vitro techniques of cell culture and organ culture as well as in vivo studies to assess the effects of potential mediators on bone resorption and bone formation. These mechanisms and factors are heterogeneous, and characterization of the pathophysiology of bone cell dysfunction in these diseases will require a broadly-based approach. Since the expertise required to identify and clarify these mechanisms will require the attention of investigators with different types of skills, a team approach will be used to unite these different approaches around the tightly focused goal of clarifying the pathophysiology of bone cell dysfunction in diseases of the oral cavity.